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Relation between age and clearance rate of nine investigational anticancer drugs from phase I pharmacokinetic data.

Abstract：

:Aging influences the disposition and effects of several classes of drugs. Although drug clearance rate is correlated with toxicity for many anticancer drugs, few data have been published concerning the relationship of aging and clearance of chemotherapy. This study was performed to identify any relationship between age and clearance rate for anticancer drugs in phase I trials at the Johns Hopkins Oncology Center. In a retrospective study, we examined the clinical and pharmacokinetic data for 344 adults (aged 21-77 years) who received 9 phase I drugs with linear clearance in 13 clinical trials. We sought correlations between age and clearance for each drug and for the whole group. Data available for 9 of the 13 trials were used to compare age (< 65 or > 65 years) versus dose delivered [< the maximum tolerated dose (MTD) vs > or = the MTD] or toxicity (< grade 3 vs > or = grade 3). Of 344 patients, 81 (23.5%) were > 65 years old, 34 (9.9%) were > or = 70 years old, and 5 (1.5%) were > or = 75 years old. There was no significant correlation between drug clearance and age for individual drugs or the group as a whole. There was no significant difference between patients of the older and younger age groups with regard to dose or toxicity. Although only a small number of patients aged > or = 75 years were treated, our results suggest that the elderly do not experience greater toxicity even when treated at doses comparable with those given younger patients and should not be excluded from phase I trials on the basis of age. As the population of the United States ages, more elderly patients will be candidates for chemotherapy. A more thorough examination of the relationships between age, clearance rate, and toxicity can be accomplished as active drugs enter phase II/III studies.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Borkowski JM,Duerr M,Donehower RC,Rowinsky EK,Chen TL,Ettinger DS,Grochow LB

doi

10.1007/BF00686507

subject

Has Abstract

pub_date

1994-01-01 00:00:00

pages

493-6

issue

eissn

0344-5704

issn

1432-0843

journal_volume

pub_type

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Relation between age and clearance rate of nine investigational anticancer drugs from phase I pharmacokinetic data.